Medicinal topical preparations can serve as drug delivery means. The vehicles thereof carry a pharmacologically active agent to the body, such as the skin, whether exposed or in an orifice or canal, or to other parts of the body by way of the skin, epidermis, epithelium and so on.
Certain skin disorders are believed to arise from inflammation or hyperproliferation of skin cells, such as, epidermal or dermal cells. Among such diseases are basal cell carcinoma, malignant melanoma, squamous cell carcinoma, actinic keratosis, Bowen's Disease, papilloma, seborrheic keratosis, eczema, allergic eczema, atopic dermatitis, ichthyosis and psoriasis.
In the case of psoriasis, a range of disorders associated therewith are known, such as, psoriasis vulgaris, guttate psoriasis, flexural psoriasis, erythrodermic psoriasis, generalized pustular psoriasis and localised pustular psoriasis.
Many of the disorders of interest are characterised by epidermal or dermal cell hyperproliferation, such as increased growth of keratinocytes. Such increased cell proliferation is associated with increased DNA synthesis, and that increased DNA synthesis can be a target for pharmacologic agents.
Eczema, also known as atopic dermatitis, relates to a variety of common skin diseases, which are characterized by itchy, red, flaking, weeping or oozing skin. Eczema is also known as skin contact allergy, seborrheic eczema, and dry skin eczema (winter itch).
Commonly used treatments for such skin disorders include local treatment with vitamin D derivatives. However, generally, Vitamin D is slow working and can cause temporary skin irritation.
Such dermatological conditions also can be treated with topical corticosteroids, which are known to have an anti-inflammatory activity, often acting at the level of the immune system. Corticosteroids also can impact carbohydrate and protein metabolism. Those conditions are commonly known as steroid-responsive dermatoses, skin disorders that improve on treatment with topical steroids.
Local treatment with steroids can be associated with thinning of the skin, easy bruising, telangiectasia, epidermal disturbances, rosacea, acne, hypertrichosis, hypopigmentation, stretch marks among other unwanted side effects. (Hengge et al., J Am Acad Dermatol 54:1-15, 2006; Del Rosso & Friedlander, J Am Acad Dermatol 53:S50-58, 2005; and Beltrani et al., Immunol Allergy Clin N Am 25:557-580, 2005) Furthermore, administration of steroids can result in a rebound phenomenon, an exaggerated body response to terminating steroid treatment.
In controlled clinical trials, various adverse reactions to steroid therapy commonly are observed, including local burning, pruritus, local dryness, local pain, hyperpigmentation around resolving plaque, irritation and atrophy. A clobetasol propionate spray is not recommended for use on individuals younger than 18 years of age, treatment should be limited to 2 consecutive weeks, the total dosage should not exceed 50 g (59 mL or 2 fl oz) per week, the spray should not be used on the face, or in the groin or axillae, and patients should use the spray only for the minimum period necessary to achieve desired results.
Of importance is the impact such topical steroids can have at remote sites in the body. For example, clobetasol propionate is known to suppress the hypothalamus-pituitary-adrenal (HPA) axis at effective and prescribed doses. That can lead to reduced cortisol secretion resulting from a reduced amount of CRH. Abrupt withdrawal of exogenous steroids may precipitate an adrenal crisis. Gulliver & Eid, Immunol Allergy Clin N Am 25:541-555, 2005; Yawalkar et al., J Am Acad Dermatol 25:1137-1144, 1991.
Because of the impact of exogenous steroids on the pituitary, hypothalamus and adrenal glands, which can lead to range of systematic sequellae arising from the impact of hormones, such as, the adrenal hormones, on various tissues in the body, containing exogenous steroids at the site needed, such as the skin, is important to minimize unwanted systemic side effects.
Topical steroids commonly are divided into groups according to strength, see, for example, Hengge et al., supra. Very potent steroids (up to 600 times as potent as hydrocortisone) include clobetasol propionate and betamethasone dipropionate. Potent steroids (50-100 times as potent as hydrocortisone) include betamethasone valerate, diflucortolone valerate, hydrocortisone 17-butyrate, mometasone furoate and methylprednisolone aceponate. Moderate steroids (2-25 times as potent as hydrocortisone) include clobetasone butyrate and triamcinolone acetonide. The methods for assessing the strength of a steroid are known and are recognized by regulatory and international health care agencies, such as, the US FDA and WHO, see, also, Habif, Clinical Dermatology. 1990. Mosby. Inside of the front cover.
Thus, there remains a need in the art for a therapeutic product and approach that can contain and deliver one or more active agents or medicines using a vehicle with beneficial properties for use on keratinized skin or on mucosa. Such a liquid vehicle, for example, an oil, a thin gel, a spirit, a tincture, a suspension, a splash and the like would be one that can carry an effective pharmacologic agent for treating skin inflammation diseases with minimal adverse impact, and that has a non-drying, moisturizing and/or penetrating effect on human skin.